CATALYST, MECHANISM, AND REACTION DEVELOPMENT IN ACRIDINIUM AND FLAVIN PHOTOREDOX CATALYSIS Ian Andrew MacKenzie A dissertation submitted to the faculty of The University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry. Chapel Hill 2019 Approved by: David A. Nicewicz Simon J. Meek Sidney M. Wilkerson-Hill Michel R. Gagné Gerald J. Meyer © 2019 Ian Andrew MacKenzie ALL RIGHTS RESERVED ii ABSTRACT Ian Andrew MacKenzie: Catalyst, Mechanism, and Reaction Development in Acridinium and Flavin Photoredox Catalysis (Under the direction of David A. Nicewicz) The field of photoredox catalysis has grown tremendously over the past decade. This is due primarily to the wealth of new reactivity made accessible by open shell intermediates generated upon single electron transfer (SET). However, the cost of photoredox catalysts in some cases remains undesirably high. Additionally, the most well studied catalytic systems are based on precious metal photosensitizers while fully organic catalysts are significantly less developed. In the work described herein, we report on our efforts to address, in part, both of these challenges. Acridinium dyes are a class of highly oxidizing organic photoredox catalysts. Through simple design, we have synthesized a series of acridinium catalysts bearing siloxane anchoring groups for attachment onto high surface area metal oxides with the goal of recyclable catalysis. Surface loading and photostability of the catalysts are reported. High conversion for a photoredox mediated Newman-Kwart rearrangement could be achieved for one substrate with catalyst loadings less than 0.1%. Reactivity was not general and time-resolved emission studies revealed a high degree of catalyst excited state quenching upon surface attachment. Further photophysical investigations indicate an interesting and rare hole injection process as partially responsible for the observed excited state quenching. iii Immobilization of an organic flavin photocatalyst on high surface area metal oxides resulted in excellent catalytic activity. High yields for benzylic oxidation or oxygenation of a variety of alkyl benzene substrates were achieved with catalyst loadings less than 0.02%. Finally, in an effort to further characterize the acridinium class of photoredox catalysts, we investigated the photophysical properties of the one electron reduced acridyl radical. Examination of the excited state topology revealed two distinct emissive excited states, tentatively assigned as a locally excited doublet (D1) state and a twisted intramolecular charge transfer (TICT) state. Both excited states were found to be extremely reducing with the oxidation potential of the TICT state exceeding that of lithium. Application of photoexcited acridyl radical in catalysis was achieved in the reductive dehalogenation of electron rich aryl bromides and chlorides. Selective C–O cleavage of aryl methane sulfonates was also demonstrated. iv ACKNOWLEDGEMENTS It is difficult to know even where to begin in my gratitude and acknowledgements. I have deeply enjoyed my time in graduate school and have been incredibly blessed by so many people during my time here in Chapel Hill. First, I sincerely want to thank Dave for the opportunity to work in your lab and learn from you over the past four years. I am extremely grateful for your interest and willingness to take me on as a second year student switching from a different lab. I have grown tremendously as a scientist during this time and sincerely appreciate your guidance and flexibility. I want to thank my friends and coworkers in lab, past and present. You have brought laughter and a cheerful attitude to a difficult field of study. Your companionship and creative ideas have been much enjoyed. In particular, I would especially like to thank Nate Romero and Andrew Perkowski. Both of you took it upon yourselves to patiently instruct me at the bench and at the whiteboard. I am incredibly grateful for your investment in me and your continual support in my journey. To all of the many collaborators inside and outside the department I am grateful. In particular, I would mention Prateek Dongare and Degao Wang for their assistance on solid supported catalyst projects. I certainly could never have gotten started, or continued, without your help. Christian fellowship within the department has been a great source of strength for me. Kevin Olson, your friendship was a continual refreshment. Thank you for standing by me when life was hard. Kyle Brennaman, thank you for your honesty and for your deep, deep desire to be v in communion with God. Your friendship, your prayers, and your struggles have been a reminder of God’s presence and love. Outside chemistry, many others have lifted me up. Glynis Cowell, thank you for being a faithful servant of God to those around you. I am so grateful for you and for the interdepartmental fellowship group that you started. Jay and Anne Summach, thank you for loving me like your own child. Paul and Judy Gerritson, you have overwhelmed me with your love and generosity. Thank you for your continued friendship. Carolina baseball will be greatly missed. I have had a lot of good times at Boshamer Stadium. Go Heels! The music of Andrew Peterson has touched my soul. I am so grateful also for my children who were born during this time. Catherine, you are a daily joy and a wonderful little helper. I am deeply proud of you and love you dearly. Charlotte, you continually bring a smile to my face. Even at 3am when you should be asleep, and I would much prefer to be, your little face is so cute and innocent. Anne, I miss you deeply and I will always love you. I trust you to the arms of Jesus. To my parents, who will forever be Mama and Papa to me, thank you. Your love made space for me in this world and brought joy with it. Thank you for all that you have given me and for the example of Christ’s love that you continue to display. My dearest Sarah, I cannot adequately express my gratitude or my love for you. I am awed by your love and continual support. I have never and will never deserve you, but I hope that you know in some small way how great a blessing you are and how much I love you. You are my princess. vi Finally, though certainly not least, I am grateful to God. Everything that I have and am comes from You. Thank You for carrying me and for continually showing me Your love in big and little ways. Thank You for not letting go of me, ever. May You alone be honored, praised, and glorified through my work and my life. Soli Deo Gloria. vii To my wife, Sarah viii TABLE OF CONTENTS LIST OF FIGURES .................................................................................................................... xiii LIST OF SCHEMES ................................................................................................................. xvii LIST OF CHARTS .................................................................................................................... xix LIST OF TABLES ....................................................................................................................... xx LIST OF ABBREVIATIONS AND SYMBOLS ...................................................................... xxi CHAPTER 1: INTRODUCTION TO ACRIDINIUM AND FLAVIN VISIBLE LIGHT PHOTOREDOX CATALYSIS .....................................................................................................1 1.1 Introduction ........................................................................................................................1 1.2 Fundamental principles of photoredox catalysis................................................................. 2 1.2.1 Photophysical processes..............................................................................................2 1.2.2 Thermodynamics of Photoinduced Electron Transfer (PET) .................................... 3 1.2.3 Example reactions .......................................................................................................6 1.3 Development of Acridinium and Flavin Photoredox Catalysts ...........................................8 1.3.1 Evolution of Acridinium Photoredox Catalysis ..........................................................8 1.3.2 The Development of Synthetic Flavin Photoredox Catalysis ...................................11 1.4 Conclusions ........................................................................................................................14 CHAPTER 2: PROGRESS TOWARDS DEVELOPMENT OF SOLID-SUPPORTED ACRIDINIUM PHOTOCATALYSTS ......................................................................................15 2.1 Introduction ........................................................................................................................15 2.2 Results and Discussion ......................................................................................................16 2.2.1 Synthetic Efforts towards Acridiniums Functionalized with a Siloxane Anchoring Group ......................................................................................................16 2.2.2 Loading and “Dark” Stability ...................................................................................18 2.2.3 Initial Photostability Results .....................................................................................20 ix 2.2.4 Improved Photostability ............................................................................................21